OBJECTIVE: The aim of this study was to analyze the expression of apoptosis-related molecules in rheumatoid arthritis (RA) synovium, with special emphasis on the apoptosis accelerator Bax. METHODS: Immunohistochemical analysis of Bax, Bcl-2, and Bcl-x(L) was performed in tissue specimens of patients with RA and compared to normal synovial tissue. Expression of Bax was additionally determined by double labeling with CD68, p53, and Ki-67 (clone MIB-1). Apoptotic cells were further identified by the terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) method. RESULTS: In RA, expression of Bax was higher than in healthy controls and occurred in CD68-positive and -negative synoviocytes. Strong Bax staining was also found in chondrocytes at sites of cartilage degradation. Bax-positive synoviocytes could be detected with p53 and also with Ki-67. Bax and Bcl-x(L) were markedly colocalized in synovium. The TUNEL method revealed only few positive synoviocytes. CONCLUSIONS: The marked colocalization of Bax and antiapoptotic Bcl-x(L) as well as the low frequency of TUNEL-positive cells in RA synovium suggest that Bax activity is not sufficient to decrease synovial hyperplasia in RA. Apoptotic mechanisms in RA chondrocytes might also be important for the pathogenesis of joint damage.
OBJECTIVE: The aim of this study was to analyze the expression of apoptosis-related molecules in rheumatoid arthritis (RA) synovium, with special emphasis on the apoptosis accelerator Bax. METHODS: Immunohistochemical analysis of Bax, Bcl-2, and Bcl-x(L) was performed in tissue specimens of patients with RA and compared to normal synovial tissue. Expression of Bax was additionally determined by double labeling with CD68, p53, and Ki-67 (clone MIB-1). Apoptotic cells were further identified by the terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) method. RESULTS: In RA, expression of Bax was higher than in healthy controls and occurred in CD68-positive and -negative synoviocytes. Strong Bax staining was also found in chondrocytes at sites of cartilage degradation. Bax-positive synoviocytes could be detected with p53 and also with Ki-67. Bax and Bcl-x(L) were markedly colocalized in synovium. The TUNEL method revealed only few positive synoviocytes. CONCLUSIONS: The marked colocalization of Bax and antiapoptotic Bcl-x(L) as well as the low frequency of TUNEL-positive cells in RA synovium suggest that Bax activity is not sufficient to decrease synovial hyperplasia in RA. Apoptotic mechanisms in RA chondrocytes might also be important for the pathogenesis of joint damage.
Authors: John C Scatizzi; Jack Hutcheson; Richard M Pope; Gary S Firestein; Alisa E Koch; Melissa Mavers; Avraham Smason; Hemant Agrawal; G Kenneth Haines; Navdeep S Chandel; Richard S Hotchkiss; Harris Perlman Journal: Arthritis Rheum Date: 2010-02
Authors: S Busteed; M W Bennett; C Molloy; A Houston; M A Stone; F Shanahan; M G Molloy; J O'Connell Journal: Clin Rheumatol Date: 2006-03-30 Impact factor: 2.980